The increasing salinity in aquatic environments has had a negative impact on the biodegradation of atrazine, an extensively used herbicide which has been proven to pollute soil and water ecosystems. In the present study, a novel atrazine-degrading strain (ZXY-2) was isolated from industrial wastewater and identified as the Arthrobacter genus with the 16S rRNA gene. Results indicated that the strain showed a high salinity tolerance, and was able to tolerate NaCl concentrations up to 10% (w/w). Plackett–Burman (PB) multifactorial design and response surface methodology (RSM) were then employed to optimize the culturing conditions. Results showed that among the selected fifteen factors, six contributing factors were obtained. Subsequently, by employing the RSM to model and optimize atrazine degradation, a biodegradation efficiency of 12.73 mg L−1 h−1 was reached under optimal conditions (34.04 °C, pH 9.0, inoculum size 10% (v/v), 2.212 g L−1 of sucrose, 6 g L−1 of Na2HPO4·12H2O, and 50 mg L−1 of atrazine). In addition, a statistically quadratic polynomial mathematical model was suggested (R2 = 0.9873). In contrast to other atrazine-degrading bacteria, ZXY-2 appears to be adapted to life under high salinity conditions and sustains excellent atrazine degradation performance. Therefore it could potentially be applied in atrazine bioremediation.